Setting

Participants

Assessment of risk factors

MMR vaccination status was obtained from the Danish National Board of Health (compiled by general practitioner reports). Data
on birth weight, sex, gestational age, family socioeconomic status, and mother’s education were also collected.

Main outcome measures

Children’s autism status was obtained from the Danish Psychiatric Central Register; diagnoses of autistic disorder or another
autistic spectrum disorder were assigned by specialists in child psychiatry. If a child was diagnosed with both autistic disorder
and ≥1 other autistic spectrum disorder, the diagnosis was classified as autistic disorder.

Main results

The 537 303 children had follow up for a total of 2 129 864 person years. 440 655 children (82%) received the MMR vaccine;
mean age at time of vaccination was 17 months. 316 children had autistic disorder (mean age at diagnosis 4 y, 3 mo), and 422
children had other autistic spectrum disorders (mean age 5 y, 3 mo). Analysis adjusted for age, calendar period, sex, birth
weight, gestational age, mother’s education, and socioeconomic status showed that children who received the MMR vaccine did
not have an increased risk of autistic disorder or other autistic spectrum disorders compared with children who did not receive
the vaccine (table).

Conclusion

Commentary

Vaccination represents one of the great victories of preventive health care and is a major factor that separates the child
health statistics of the developed world from those of the developing world. Because vaccines are given to large numbers of
healthy children, ensuring that risk does not exceed benefit is important1 and becomes more of an issue as the risk of disease becomes very small. Parents in the developed world are not familiar with
the possible consequences of many of the diseases against which children are routinely vaccinated. This may explain why even
questionable evidence about vaccine safety generates such publicity, discussion, and disquiet.

The study by Madsen et al is further evidence that refutes a link between MMR vaccination and development of autism. The study of a large Danish sample
is important because it has the statistical power to provide stronger evidence than previous studies. The study was carefully
documented and followed up a large cohort of children, of whom 316 developed autism. The unbiased sampling strategy, completeness
of follow up, and sample size are major strengths, contrasting sharply with the report that generated many of the questions
about the relation between MMR and autism (a case series of 12 children with autism).2

Vaccination risks do exist, and parents must be informed of them. Relative risk is a complex concept; parents may not be reassured
unless a healthcare provider can assert that no risk exists, which is not possible. However, parents can easily understand
the concept of unrelated co-occurrence, which likely explains suspicions about MMR; ie, autism symptoms often occur at the
same age as MMR vaccination. Healthcare providers have a responsibility to counter unsubstantiated accusations about vaccine
safety in order to assure the safety of children in our community and the world.